The mainstream methods for cancer treatment include surgery, chemotherapy, radiation therapy, etc. Among them, surgery and radiation therapy are local therapies effective only in the parts which are surgically removed or irradiated, whereas cancer drug therapy is a systemic therapy which affects the entire body. Most cancers are diseases that occur locally and metastasize systemically, and thus a mild level of systemic metastasis is already present unless the cancer is discovered at its extremely early stage. Therefore, it is quite normal to see a high rate of cancer recurrence despite effective local therapy. In this regard, cancer drug therapy, which is especially effective in the treatment of systemically-spread cancer, is used in combination with local therapy for most cancer treatments. In cancer treatment therapies, the administration of cancer drugs is an important therapy for removing extremely small cancer tissues which are difficult to observe by the naked eye or cancer cells which have been metastasized to other tissues from their primary site, after surgical removal of the cancer region. However, it is possible that some cancers may have resistance to particular cancer drugs, or cancer cells may acquire drug resistance during long-term administration of particular cancer drugs, thus making the cancer drugs ineffective.
Chronic myeloid leukemia (CML) is a malignant bone marrow tumor characterized by the uncontrolled increase in the production of bone marrow cell clones in bone marrow cells. According to a previous report with respect to CML by the International Agency for Research on Cancer (IARC), c-abl primary cancer gene on chromosome 9 moves to a new downstream location in the 2nd exon of Bcr gene on chromosome 22, forms the Philadelphia chromosome (Ph), and expresses Bcr-Abl, a chimeric fusion protein, where the expressed fusion protein causes a series of inappropriate proliferation of blood-forming cells thus contributing to leukemic conversion. Gleevec, which is known as the most effective therapeutic agent for CML, is known to inhibit the growth of cells that express Bcr-Abl or induce apoptosis of the cells by acting through the competitive inhibition at the ATP-binding site, thereby exhibiting the effect of treating CML. However, since the disclosure that many CML patients show resistance to Gleevec (US Patent Application Publication No. 2003-0158105) was reported, there was a need for the development of a novel cancer drug capable of treating Gleevec-resistant CML, and thus studies are actively carried out for its development.
For example, WO Publication No. 2008-078203 discloses a pharmaceutical composition for treating Gleevec-resistant leukemia containing an extract of Piper betle leaves; Korean Patent Application Publication No. 2011-0055833 discloses a pharmaceutical composition for treating Gleevec-resistant leukemia containing 3-hydroxyflavone as an active ingredient; and Korean Patent Application Publication No. 2014-0127985 discloses a pharmaceutical composition for treating Gleevec-resistant leukemia containing an extract of yellow poplar cortex. Since these pharmaceutical compositions are mostly derived from natural products, they have an advantage in that they exhibit effects of treating Gleevec-resistant leukemia while being capable of minimizing their side-effects. However, these pharmaceutical compositions also have a problem in that they require long-term administration due to their poor therapeutic effects against Gleevec-resistant leukemia. Accordingly, there is a need for the development of a therapeutic agent which can exhibit excellent therapeutic effects for Gleevec-resistant leukemia with minimal side-effects.